Programmed death-1 ligand (PD-L)1 and PD-L2 are ligands for programmed death-1 (PD-1), a member of the CD28/CTLA4 family expressed on activated lymphoid cells. PD-1 contains an immunoreceptor ...tyrosine-based inhibitory motif and mice deficient in PD-1 develop autoimmune disorders suggesting a defect in peripheral tolerance. Human PD-L1 and PD-L2 are expressed on immature dendritic cells (iDC) and mature dendritic cells (mDC), IFN-gamma-treated monocytes, and follicular dendritic cells. Using mAbs, we show that blockade of PD-L2 on dendritic cells results in enhanced T cell proliferation and cytokine production, including that of IFN-gamma and IL-10, while blockade of PD-L1 results in similar, more modest, effects. Blockade of both PD-L1 and PD-L2 showed an additive effect. Both whole mAb and Fab enhanced T cell activation, showing that PD-L1 and PD-L2 function to inhibit T cell activation. Enhancement of T cell activation was most pronounced with weak APC, such as iDCs and IL-10-pretreated mDCs, and less pronounced with strong APC such as mDCs. These data are consistent with the hypothesis that iDC have a balance of stimulatory vs inhibitory molecules that favors inhibition, and indicate that PD-L1 and PD-L2 contribute to the poor stimulatory capacity of iDC. PD-L1 expression differs from PD-L2 in that PD-L1 is expressed on activated T cells, placental trophoblasts, myocardial endothelium, and cortical thymic epithelial cells. In contrast, PD-L2 is expressed on placental endothelium and medullary thymic epithelial cells. PD-L1 is also highly expressed on most carcinomas but minimally expressed on adjacent normal tissue suggesting a role in attenuating antitumor immune responses.
Abstract
Background and Objectives
Sustained implementation of new programs in complex care systems like nursing homes is challenging. This prospective qualitative evaluation examined factors ...affecting the sustainability of the Staff Training in Assisted Living Residences in Veterans Health Administration (STAR-VA) program in Veterans Health Administration (VA) Community Living Centers (CLC, i.e., nursing homes). STAR-VA is an evidence-based interdisciplinary, resident-centered, behavioral approach for managing distress behaviors in dementia.
Evaluation Design and Methods
In 2019, we conducted 39 semistructured phone interviews with STAR-VA key informants across 20 CLCs. We identified a priori themes based on the Organizational Memory Framework, which includes 7 Knowledge Reservoirs (KRs): people, routines, artifacts, relationships, organizational information space, culture, and structure. We conducted content-directed analysis of transcripts to identify factors to program sustainment.
Results
We identified 9 sustainment facilitators across KRs: engaged site leaders and champions, regular meetings and trainings, written documentation and resources, regular and open communication, available educational tools (e.g., handouts and posters), adequate spaces, leadership support on many levels, staff buy-in across disciplines, and staff competencies and recognition. Ten barriers across KRs included: staffing concerns, inconsistent/inefficient routines, inconsistent documentation, lack of written policies, communication gaps, nonstandardized use of tools, constraints with meeting spaces and regulations on posting information, limited leadership support, division among staff, and missing performance expectations.
Discussion and Implications
Findings inform tailored strategies for optimizing STAR-VA program sustainment in CLCs, including the development of a sustained implementation guide, implementation resources, regional communities of practice, and STAR-VA integration into national CLC quality improvement routines for team communication and problem-solving.
Global policies on disaster risk reduction have highlighted individual and community responsibilities and roles in reducing risk and promoting coping capacity. Strengthening local preparedness is ...viewed as an essential element in effective response and recovery. This paper presents a synthesis of available literature on household preparedness published over the past 15 years. It emphasizes the complexity of preparedness, involving personal and contextual factors such as health status, self-efficacy, community support, and the nature of the emergency. In addition, people require sufficient knowledge, motivation and resources to engage in preparedness activities. Social networks have been identified as one such resource which contributes to resilience. A predominant gap in the literature is the need for evidence-informed strategies to overcome the identified challenges to household preparedness. In particular, the construct of social capital and how it can be used to foster individual and community capacity in emergency situations requires further study.
The Communal Coping Model of pain catastrophizing proposes that pain catastrophizers enact pain behaviors in order to solicit support or empathy from their social environment. By this account, pain ...catastrophizers might be expected to engage in behavior aimed at maximizing the probability that their pain will be perceived by others in their social environment. To test this prediction, 40 undergraduates were videotaped during a cold pressor procedure. A separate sample of 20 (10 men, 10 women) undergraduates were asked to view the video sequences and infer the pain ratings of the cold pressor participants. Correlational analyses revealed that higher levels of pain catastrophizing of the cold pressor participants were associated with observer inferences of more intense pain, r=.39, p<.01. The relation between cold pressor participants' level of pain catastrophizing and observer inferences of pain intensity was mediated by the cold pressor participants' pain behavior. Although pain catastrophizing was associated with observers' inferences of more intense pain, cold pressor participants' level of pain catastrophizing was not associated with observers' accuracy in inferring self-reported pain. Implications of the findings for theory and clinical practice are addressed.
The objective of this study was to test and revise a staff assessment of person-centered care (PCC) within the Veterans Health Administration (VA) Community Living Center (CLC) setting.
Starting with ...measures of PCC initially developed through the Better Jobs Better Care (BJBC) study, we conducted cognitive interviews with CLC staff to assess applicability to the VA setting. We then (a) modified the questionnaire based on respondent feedback, (b) administered the revised survey via Internet to 265 staff at 8 VA CLCs, and (c) examined the psychometric properties of the revised 50-item BJBC PCC instrument using multitrait analysis.
Scale reliabilities met the criterion for group comparisons (alpha levels ranged from 0.84 to 0.91). The pattern of item correlations and intra- and interscale correlations indicating convergent and discriminant validity, respectively, were both 100%.
Our results support the broader use of the BJBC survey within VA. In addition, given the high levels of internal consistency reliability of the current scales, it is likely that a psychometrically sound short form of the instrument could be created. Further research on construct and convergent validity are warranted to support the broader application of the instrument.
Evidence-based practices to manage distress behaviors in dementia (DBD) are not consistently implemented despite demonstrated effectiveness. The Veterans Health Administration (VA) trained teams to ...implement Staff Training in Assisted Living Residences (STAR)-VA, an intervention to manage DBD in VA nursing home settings, or Community Living Centers (CLCs). This paper summarizes multiyear formative evaluation results including challenges, adaptations, and lessons learned to support sustained integration into usual care across CLCs nationwide.
STAR was selected as an evidence-based practice for DBD, adapted for and piloted in VA (STAR-VA), and implemented through a train-the-trainer program from 2013 to 2018. Training and consultation were provided to 92 CLC teams. Evaluation before and after training and consultation included descriptive statistics of measures of clinical impact and survey feedback from site teams regarding self-confidence, engagement, resource quality, and content analysis of implementation facilitators and challenges.
STAR-VA training and consultation increased staff confidence and resulted in significant decreases in DBD, depression, anxiety, and agitation for Veterans engaged in the intervention. Implementation outcomes demonstrated feasibility and identified facilitators and barriers. Key findings were interpreted using implementation frameworks and informed subsequent modifications to sustain implementation.
STAR-VA successfully prepared teams to manage DBD and resulted in improved outcomes. Lessons learned include importance of behavioral health-nursing partnerships, continuous engagement, iterative feedback and adaptations, and sustainment planning. Evaluation of sustainment factors has informed selection of implementation strategies to address sustainment barriers. Lessons learned have implications for integrating team-based practices into system-level practice.
We identify factors associated with sustainment of an intervention (STAR-VA) to address distress behaviors in dementia (DBD), guided by the Organizational Memory Knowledge Reservoir (KR) framework, ...compared across 2 types of outcomes: (1) site performance improvement on a clinical outcome, the magnitude of change in levels of DBD, and (2) self-rated adherence to STAR-VA core components, a process outcome.
We used a cross-sectional sequential explanatory mixed methods design guided by the Organizational Memory Framework.
We selected 20 of 79 sites that completed STAR-VA training and consultation based on rankings on 2 outcomes-change in an indicator of DBD and reported adherence to STAR-VA core components. We recruited key informants most knowledgeable about STAR-VA resulting in a sample of 43% behavioral coordinators, 36% nurse champions, and 21% nurse leaders.
We collected data with key informants at each Community Living Center (CLC) from December 2018 to June 2019. We analyzed data using within-case and cross-case matrixes created from the coded transcripts for each a priori KR domain. We then assessed if there were any similarities or differences for CLCs in comparable DBD performance and STAR-VA adherence categories.
We found 4 KRs that differentiated sustainment factors based on CLC implementation process and clinical outcomes-3 KRs related to DBD performance (people, relationships, and routines) and 2 related to STAR-VA adherence (relationships and culture).
This evaluation found several knowledge retention mechanisms that differ in high and low performance/adherence sites. Our findings highlight knowledge retention/sustainment strategies based on site functioning to support sustainment strategies in the CLC. Understanding sustainment factors as they relate to clinical and process outcomes is innovative and can be used to support CLCs struggling with sustainment. More research is needed to inform tailored sustainment efforts based on site functioning in the nursing home setting.
Positional cloning of hereditary deafness genes is a direct approach to identify molecules and mechanisms underlying auditory function. Here we report a locus for dominant deafness, DFNA36, which ...maps to human chromosome 9q13-21 in a region overlapping the DFNB7/B11 locus for recessive deafness. We identified eight mutations in a new gene, transmembrane cochlear-expressed gene 1 (TMC1), in a DFNA36 family and eleven DFNB7/B11 families. We detected a 1.6-kb genomic deletion encompassing exon 14 of Tmc1 in the recessive deafness (dn) mouse mutant, which lacks auditory responses and has hair-cell degeneration. TMC1 and TMC2 on chromosome 20p13 are members of a gene family predicted to encode transmembrane proteins. Tmc1 mRNA is expressed in hair cells of the postnatal mouse cochlea and vestibular end organs and is required for normal function of cochlear hair cells.
In this paper, by the use of X-ray photoelectron spectroscopy, we unequivocally identify the oxides present on GaAs surfaces and accurately measure the binding energies associated with the 2p
3/2, ...3d, and Auger lines in the X-ray photoemission spectra. These measurements intended to provide reliable reference data for further work. We conducted an extensive analysis of the oxidation states of Ga metal and oxide powder reference samples, air exposed GaAs wafers, and wafers subjected to various surface treatments (argon plasma treatments and boiling). Based on this experimental evidence, an assignment of the photoelectron peaks to various chemical states is proposed.
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